lts suggest that SLAMF3 expression in hepatocytes primarily controls cell proliferation through MAPK, ERK and JNK inhibition and induces apoptosis through 852808-04-9 caspase pathway. However, additional experiments are required to pinpoint the involvement of BCL2 family members in SLAMF3-dependent apoptosis. Furthermore, it has been firmly established that constitutive activation of the PI3K/AKT/mTOR signalling pathway is a determinant of tumour cell growth and survival in many different solid tumours. This pathway can be hyper activated by enhanced stimulation of receptor tyrosine kinases such as the insulin-like growth factor receptor and epidermal growth factor receptor. EGF receptor in particular whose expression is upregulated in HCC and human cirrhotic liver points out towards hyperactivation of PI3K/AKT/mTOR pathway in both conditions. As reported elsewhere, mTOR activation increases cell proliferation, whereas the blockade of mTOR signalling by rapamycin analogues slows tumour growth and increases survival in the HCC xenograft model. These findings suggest that mTOR pathway activation has a crucial role in the pathogenesis of HCC. Based on this observation we investigated the link between effect of SLAMF3 expression on proliferation and activation of mTOR and found that SLAMF3 expression had an inhibitory effect on mTOR phosphorylation in a PI3K-and AKT-activation-independent manner. The restoration of higher SLAMF3 expression in HCC cells may indirectly control the activation of mTOR by inhibiting Erk phosphorylation without affecting the PI3K/AKT pathways. Furthermore, it has also been reported that mTOR is activated through the ERK pathway as well as through the AKT pathway. The effector kinases in the mTOR pathway activation are AKT, ERK1/2 and ribosomal S6 kinase RSK1, which phosphorylates and inactivates tuberous sclerosis complex 1/2 and activates mTOR on serine 2448. The molecular partners linking SLAMF3, ERK/JNK and mTOR have yet to be identified in hepatocytes. Interestingly, restoration of SLAMF3 expression in HCC cells reduced cell migration and the rearrangement of cytoskeletal elements, a phenomenon associated with the promotion of metastasis and the migration of neoplastic cells. SLAMF3 comprises of four extracellular Ig-like domains. 1403254-99-8 cost Domains 1 and
